The role of histamine H1 receptor and H2 receptor in LPS-induced liver injury

To examine the role of histamine H-1 and H-2 receptors in the regulation of lipopolysaccharide ( LPS)- induced liver injury, a combination of D- galactosamine and LPS ( GalN/ LPS) was administered to histamine H-1 receptor knockout ( H-1- R KO) and H-2 receptor knockout ( H-2- R KO) mice. The numbers of necrotic and apoptotic hepatocytes in the liver, as well as the levels of serum aspartate transaminase ( AST) and alanine transaminase ( ALT), were increased significantly by GalN/ LPS treatment compared to the appropriate controls. Pretreatment with histamine ameliorated the GalN/ LPS- induced necrotic and apoptotic changes in the hepatocytes and inhibited the elevation of serum AST and ALT levels. Histamine attenuated the GalN/ LPS- induced increases in the levels of TNF- alpha, but augmented those of IL- 10 both in the liver and serum. Histamine inhibited the GalN/ LPS- induced caspase- 3 activity in the liver. Furthermore, these effects of histamine were completely or partially attenuated in H-2- R KO mice, but not in H-1- R KO mice. Peritoneal macrophages from H-2- R KO mice exhibited blunted changes in the effects of histamine on LPS- induced TNF- alpha and IL- 10 production in vitro compared to the wild- type ( WT) controls. In summary, the present findings suggest that the histamine H-2- R- TNF- alpha and - IL- 10 pathways play protective roles in endotoxin- induced hepatic injury.